Search

The purpose of this study was to evaluate a theory-based, multicomponent eHealth intervention aimed at improving child health behaviors and parental psychosocial attributes and feeding practices. A pilot randomized controlled trial was conducted among 73 parents with children (1–3 years). Intervention group participants (IG, n = 37) received theory-based educational videos, cooking tutorials, and text messages with key information for a total of 8 weeks. Control group participants (CG, n = 36) received a booklet about general nutrition recommendations for children. A parent-administered questionnaire was used for data collection at baseline and post-intervention. Linear models were performed using R version 4.1.1. for data analysis. Children in the IG significantly increased their daily intake of fruit (ΔΔ = 0.89 servings, p = 0.00057) and vegetables (ΔΔ = 0.60 servings, p = 0.0037) and decreased use of screen time (ΔΔ = −33.87 min, p = 0.026), compared to the CG. Parents in the IG improved significantly more than the CG in self-efficacy (p = 0.0068) and comprehensive feeding practices (p = 0.0069). There were no significant differences between the study groups for changes in child outcomes, such as physical activity and sedentary behaviors, and parental nutrition knowledge and attitudes.

ImportanceStudies have suggested that greater primary care physician (PCP) availability is associated with better population health and that a diverse health workforce can improve care experience measures. However, it is unclear whether greater Black representation within the PCP workforce is associated with improved health outcomes among Black individuals.ObjectiveTo assess county-level Black PCP workforce representation and its association with mortality-related outcomes in the US.Design, Setting, and ParticipantsThis cohort study evaluated the association of Black PCP workforce representation with survival outcomes at 3 time points (from January 1 to December 31 each in 2009, 2014, and 2019) for US counties. County-level representation was defined as the ratio of the proportion of PCPs who identifed as Black divided by the proportion of the population who identified as Black. Analyses focused on between- and within-county influences of Black PCP representation and treated Black PCP representation as a time-varying covariate. Analysis of between-county influences examined whether, on average, counties with increased Black representation exhibited improved survival outcomes. Analysis of within-county influences assessed whether counties with higher-than-usual Black PCP representation exhibited enhanced survival outcomes during a given year of heightened workforce diversity. Data analyses were performed on June 23, 2022.Main Outcomes and MeasuresUsing mixed-effects growth models, the impact of Black PCP representation on life expectancy and all-cause mortality for Black individuals and on mortality rate disparities between Black and White individuals was assessed.ResultsA combined sample of 1618 US counties was identified based on whether at least 1 Black PCP operated within a county during 1 or more time points (2009, 2014, and 2019). Black PCPs operated in 1198 counties in 2009, 1260 counties in 2014, and 1308 counties in 2019—less than half of all 3142 Census-defined US counties as of 2014. Between-county influence results indicated that greater Black workforce representation was associated with higher life expectancy and was inversely associated with all-cause Black mortality and mortality rate disparities between Black and White individuals. In adjusted mixed-effects growth models, a 10% increase in Black PCP representation was associated with a higher life expectancy of 30.61 days (95% CI, 19.13-42.44 days).Conclusions and RelevanceThe findings of this cohort study suggest that greater Black PCP workforce representation is associated with better population health measures for Black individuals, although there was a dearth of US counties with at least 1 Black PCP during each study time point. Investments to build a more representative PCP workforce nationally may be important for improving population health.

Background Social isolation or living alone can negatively affect mental health, sleep quality, eating behavior, immunity, proinflammatory response to stress, and receipt of care in cancer patients (e.g., assistance with nutrition and mobility, emotional and informational support), which may increase the risk of death from cancer. Previous studies, however, have shown inconsistent findings on the association between social isolation and cancer mortality. To address the literature gap, we examined this association among working-age adults stratified by sociodemographic characteristics using a nationally representative cohort with long-term mortality follow-up. Method We used the pooled 1998-2019 data for adults aged 18-64 years at enrollment from the National Health Interview Survey (NHIS) linked to National Death Index (N=473,648) with up to 22 years of follow-up. Cox proportional hazards regression was used to model survival time as a function of social isolation, measured by “living alone”, and sociodemographic, behavioral, and health characteristics. We estimated differential effects of social isolation on cancer mortality by age, sex, race/ethnicity, poverty level, and education, overall and for select common cancers (lung, colorectal, and female breast) with >100 deaths in the public use NHIS-linked mortality database, 1998-2004. Results The cancer mortality risk was 32% higher (hazard ratio [HR]=1.32; 95%CI:1.25,1.39) in adults living alone, controlling for age, and 16% higher (HR=1.16; 95%CI:1.10,1.23) in adults living alone, controlling for demographic and socioeconomic characteristics, when compared to adults living with others. The association between living alone and cancer mortality persisted after additional adjustments for health-risk behaviors and health status (HR=1.10, 95%CI:1.04,1.16). Stratified models generally showed similar associations between social isolation and cancer mortality risk across categories of sex, poverty, and education in age-adjusted models. However, the association was stronger among non-Hispanic (NH) White than NH Black adults and did not exist in other racial/ethnic groups. The associations were attenuated after additional adjustments but persisted in fully adjusted models among males, females, NH White people, and adults with a college degree. In the age-adjusted models, social isolation was associated with a higher risk of death from lung (HR=1.45; 95%CI:1.81,2.45) and colorectal (HR=1.65; 95%CI:2.58,1.56), but not from female breast cancer. Conclusions In this nationally representative study in the United States, adults living alone were at a higher risk of cancer death compared to adults living with others. These findings underscore the significance of addressing social isolation in the general population and among cancer survivors. Citation Format: Hyunjung Lee, Gopal K. Singh, Ahmedin Jemal, Farhad Islami. Differential effects of social isolation on cancer mortality by race/ethnicity and socioeconomic status among working age adults in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1927.

Background: The lesbian, gay, bisexual, and transgender (LGBT) population comprises approximately 5.6% of the total US population. Levels and patterns of psychological distress in the LGBT population are less well known compared with the general population. This study examines the prevalence and sociodemographic and behavioral correlates of psychological distress among lesbian, gay, and bisexual (LGB) adults in the United States. Methods: Using the pooled cross-sectional data from the 2013-2018 National Health Interview Surveys (N=183,020), differentials in serious psychological distress (SPD) and factor-based psychological distress scores were analyzed by multivariate linear and logistic regression. Results: The prevalence of SPD was 8.0% for the LGB population aged ≥18, 7.0% for gay and bisexual males, and 8.9% for LGB females, compared with 3.4% for the total straight/heterosexual population, 2.7% for straight males, and 4.0% for straight females. Mean psychological distress index scores were highest among LGB females (109.8), followed by gay and bisexual males (105.8), straight females (100.6), and straight males (97.7). Compared with the straight population, LGB adults had higher education, unemployment, and poverty levels and were more likely to be non-Hispanic White and single. LGB adults were more likely to smoke and drink alcohol and more likely to be physically active than straight adults. LGB females had higher obesity but gay and bisexual males had lower obesity rates than their straight counterparts. After controlling for covariates, LGB adults had 89% higher odds of SPD and significantly higher distress levels than straight adults. Younger age, lower-income, divorce/separation, lack of health insurance, functional limitation, smoking, physical inactivity, and obesity were significant predictors of SPD and higher psychological distress levels in LGB adults. Conclusion and Implications for Translation: Significant disparities in mental health exist, with LGB adults at substantially increased risk of psychological distress and likely in greater need of appropriate social and mental health services. Health policies aimed at improving the material conditions and social environments may lead to improved mental health outcomes among LGB adults and the general population. Copyright © 2022 Singh, et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

Background: The lesbian, gay, bisexual, and transgender (LGBT) population makes up approximately 6% of the total United States (US) population. Levels and patterns of food insecurity in the LGBT population during the COVID-19 pandemic compared with the general population are unknown. This study examines prevalence and sociodemographic correlates of food insecurity among LGBT and straight/heterosexual adults in the US. Methods: Using the US Census Bureau’s Household Pulse Survey from July to October 2021 (N=372,542), differentials in food insecurity according to LGBT status were analyzed by multivariate logistic regression. Results: The prevalence of food insecurity during the pandemic was 25.6% for transgender adults aged ≥18, significantly higher than that for lesbian/gay adults (11.6%), bisexual adults (13.5%), and straight/heterosexual adults (7.8%). Compared with the straight/heterosexual population, LGBT adults had lower education and income levels and higher unemployment and were more likely to be non-Hispanic White and single. Transgender adults were particularly disadvantaged with respect to socioeconomic status, job loss, and lack of health insurance. After controlling for socioeconomic and demographic covariates, lesbian/gay, bisexual, and transgender adults experienced, respectively, 36%, 35%, and 157% higher odds of food insecurity than straight/heterosexual adults. Black/African American, Hispanic, and mixed-race/ethnicity, lower education and income, lack of homeownership, divorce/separation, lack of health insurance, and recent job loss were significant predictors of food insecurity among LGBT adults. Inequalities in food insecurity by LGBT status were similar in large metropolitan areas. Conclusions and Implication for Translation: Significant disparities in food insecurity exist withLGBT adults, particularly transgender adults, at substantially increased risk of experiencing food insecurity, economic hardship, and social disadvantage during the pandemic and likely in greater need of social and public assistance. Health policies aimed at improving the social and material conditions may lead to improved food security and health outcomes among LGBT adults and the general US population. Copyright © 2022 Singh et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

Skeletal muscle atrophy is characterized by reduced muscle function and size. Oxidative stress contributes to muscle atrophy but can be treated with antioxidants. This study investigated the antioxidant activity of a castor oil plant leaf (

This study aimed to optimize the emulsification of olive oil in chicken sausage production at varying cutting times (30, 45, and 60 s) and cooking temperatures (63, 73, and 83°C). Pork backfat sausages were prepared as controls, using the same variables. The quality attributes of the sausages were analyzed, and the distribution of lipid droplets was identified using confocal laser scanning microscopy. The combinations of cutting time and cooking temperature in olive oil sausages showed different emulsifying characteristics. Meat emulsion with olive oil at a cutting time of 60 s and cooking temperature of 73°C showed the highest emulsion stability with lowest water and lipid loss (2.49%, P < 0.05). The pH values were lower for olive oil samples than for the controls (5.9 vs. 6.2, P < 0.05). Cutting time of 60 s and cooking temperature of 73°C generated higher hardness, gumminess, and chewiness in olive oil sausages (P < 0.05). The replacement of pork backfat with olive oil resulted in a higher b*, C*, and h values, as well as lower lipid oxidation (P < 0.05). In addition, microstructural images exhibited a finer distribution of lipid droplets in olive oil sausages with a cutting time of 60 s. In conclusion, chicken sausage at a cooking temperature of 73°C and cutting time of 60 s was optimal for producing sausages with olive oil. Given the condition, the sausages produced from olive oil had better emulsion and oxidative stability than sausages produced from pork backfat.

Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/β-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/β-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of β-catenin compared with diminished nuclear PPARγ levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the β-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.

This systematic review and meta-analysis examined previous studies on music-based interventions for individuals with Parkinson’s disease (PD). The effectiveness of the interventions on various motor and non-motor outcomes was evaluated. This review was conducted by searching PubMed, CINAHL, PsycINFO, and Cochrane Library CENTRAL prior to June 2022 for randomized controlled trial (RCT) and controlled clinical trial (CCT) studies published in English. Data were expressed as weighted/standardized mean difference (MD/SMD) with 95% confidence intervals (CI). I2 index was used for heterogeneity. The initial search identified 745 studies, and 13 studies involving 417 participants with PD which met the inclusion criteria included in this review. The results of the meta-analysis revealed that music-based interventions can significantly improve walking velocity (MD = 0.12, 95% CI = 0.07~0.16, p < 0.00001), stride length (MD = 0.04, 95% CI = 0.02~0.07, p = 0.002), and mobility (MD = −1.05, 95% CI = −1.53~−0.57, p < 0.0001). However, the results did not support significant effects for music-based interventions on cadence (MD = 3.21, 95% CI = −4.15~10.57, p = 0.39), cognitive flexibility (MD = 20.91, 95% CI = −10.62~52.44, p = 0.19), inhibition (SMD = 0.07, 95% CI = −0.40~0.55, p = 0.76), and quality of life (SMD = −0.68, 95% CI= −1.68~0.32, p = 0.18). The findings suggest that music-based interventions are effective for the improvement of some motor symptoms, but evidence for non-motor symptoms is limited. Further high-quality studies with a larger sample size are required to obtain the robust effects of music-based interventions on various outcomes among patients with PD.

This study aimed to identify the level of mothers’ smartphone dependency and determine its correlation with preschoolers’ problem behavior and emotional intelligence. From 1 November to 30 December 2020, 141 mothers of preschool children (aged three to six years) were recruited to complete questionnaires that assessed their smartphone dependency and their child’s problem behavior and emotional intelligence. The result revealed that the younger the mother and the higher the perception of boredom in daily living, the higher was the level of her smartphone dependency. Maternal smartphone dependency was also significantly correlated with the aggression, oppositional, and emotional instability subscales of the tool assessing children’s problem behavior. To prevent problem behaviors among preschoolers, strategies to reduce mothers’ smartphone dependency are needed.

Significant progress has been made on the molecular biology of the severe fever with thrombopenia virus (SFTSV); however, many parts of the pathophysiological mechanisms of mortality in SFTS remain unclear. In this study, we investigated virologic and immunologic factors for fatal outcomes of patients with SFTS. We prospectively enrolled SFTS patients admitted from July 2015 to October 2020. Plasma samples were subjected to SFTSV RNA RT-PCR, multiplex microbead immunoassay for 17 cytokines, and IFA assay. A total of 44 SFTS patients were enrolled, including 37 (84.1%) survivors and 7 (15.9%) non-survivors. Non-survivors had a 2.5 times higher plasma SFTSV load than survivors at admission (p < 0.001), and the viral load in non-survivors increased progressively during hospitalization. In addition, non-survivors did not develop adequate anti-SFTSV IgG, whereas survivors exhibited anti-SFTSV IgG during hospitalization. IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF were significantly elevated in non-survivors compared to survivors and did not revert to normal ranges during hospitalization (p < 0.05). Severe signs of inflammation such as a high plasma concentration of IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF, poor viral control, and inadequate antibody response during the disease course were associated with mortality in SFTS patients.

The globalization of art therapy requires a high level of multicultural competence among art therapists for ethical practice, which includes understanding the traditional materials of the client’s ...

In this study, we found that nuclear receptors FXR and LXR (originally characterized as regulatory factors involved in cholesterol/bile acid homeostasis) regulate the expression of Oct3/4, a marker for cell differentiation, in both normal renal-derived cell line HK-2 and renal adenocarcinoma cell line ACHN. Down-regulation of Oct3/4 expression by activating FXR and LXR occurs only in normal renal cell-derived HK-2 cells. We also found that the RNA-binding protein, ELAVL2, oppositely regulates Oct3/4 expressions in HK-2 and ACHN cells. Moreover, we revealed that LXR-alpha and LXR-beta regulate each other's expression. Although an LXR-beta-specific agonist is assumed to be the basis for an anti-arteriosclerotic drug that only stimulates reverse cholesterol transport, our findings show that the development of such an anti-arteriosclerotic drug would require further elucidation of the complex mechanism of LXR-alpha and LXR-beta regulation.

The gut microbiome influences the health and well-being of dogs. However, little is known about the impact of breed on the fecal microbiome composition in dogs. Therefore, we aimed to investigate the differences in the fecal microbiome in three breeds of dog fed and housed under the same conditions, namely eight Maltese (8.0 ± 0.1 years), eight Miniature Schnauzer (8.0 ± 0.0 years), and nine Poodle dogs (8.0 ± 0.0 years). Fresh fecal samples were collected from the dogs and used to extract metagenomic DNA. The composition of the fecal microbiome was evaluated by 16S rRNA gene amplicon sequencing on the MiSeq platform. A total of 840,501 sequences were obtained from the 25 fecal samples and classified as Firmicutes (32.3-97.3% of the total sequences), Bacteroidetes (0.1-62.6%), Actinobacteria (0.2-14.7%), Fusobacteria (0.0-5.7%), and Proteobacteria (0.0-5.1%). The relative abundance of Firmicutes was significantly lower in the Maltese dog breed than that in the other two breeds, while that of Fusobacteria was significantly higher in the Maltese than in the Miniature Schnauzer breed. At the genus level, the relative abundance of Streptococcus, Fusobacterium, Turicibacter, Succinivibrio, and Anaerobiospirillum differed significantly among the three dog breeds. These genera had no correlation with age, diet, sex, body weight, vaccination history, or parasite protection history. Within a breed, some of these genera had a correlation with at least one blood chemistry value. This study indicates that the composition of the fecal microbiome in dogs is affected by breed.

We demonstrate the fabrication of a large area 2-dimensional (2-D) binary colloidal assembly of polymeric microspheres (μ-spheres) and TiO2 nanoparticles (NPs). TiO2 NPs near the surface of poly(me...

Senile osteoporosis increases the risk of skeletal fractures with age. Cheonggukjang (CGJ), a traditional Korean dry fermented soybean product, has numerous therapeutic effects; however, its effects on bone mineral density (BMD) and bone metabolism in senile osteoporosis are unclear. In this study, we treated the senescence-accelerated mouse prone 6 (SAMP6) model of senile osteoporosis with CGJ to determine its potential for ameliorating and preventing osteoporosis progression. High-performance liquid chromatography analysis for isoflavone profiles revealed that short-term fermentation significantly increased the isoflavone aglycone content in soybeans. Thereafter, we fed 6-week-old SAMP6 mice with experimental diets containing 5% or 10% CGJ for 15 weeks. Microcomputed tomography revealed that CGJ supplementation effectively increased the BMD and relative bone length. In vitro, CGJ increased the osteopontin reactivity and upregulated the expression of Alp, Col1a1, Fak, Bmp2/4, Smad1/5/8, and Runx2 in osteoblasts, and decreased Cathepsin K reactivity and downregulated Rankl and Nfatc1 expression in osteoclasts. In addition, CGJ increased the osteoprotegerin/Rankl ratio. Collectively, these results demonstrate that CGJ can ameliorate the detrimental effects of senile osteoporosis by improving osteogenesis and decreasing osteoclast activity.

A conceptual design study for a steady-state Korean fusion demonstration reactor (K-DEMO) was initiated in 2012. The superconducting magnet system is one of the key components of the K-DEMO and the preliminary study on superconducting magnet system has been done in 2015. The superconducting magnet system of K-DEMO consists of 16 TF (Toroidal Field), 8 CS (Central Solenoid) and 12 PF (Poloidal Field) coils. All of the TF, CS and PF coils use internally-cooled Cable-In-Conduit Conductors (CICC). A high performance Nb3Sn-based conductor, an ITER-type Nb3Sn and NbTi conductor will be used for the magnet. Based on the preliminary design, continuous design study is being performed and the K-DEMO magnet system has been evolved mainly for solving engineering issues. Two issues were considered for the TF, the reinforcement of the low field TF CICC structure and the fabrication stability of the high field TF CICC. In the CS magnet, reducing the number of Helium feed-throughs was a main issue. A small change has been made for the PF magnets for keeping a void fraction of the PF conductor. In this work, the major parameters and design updates of the K-DEMO magnet system is presented.

Wavelength-selective, nanostructured metallic radiation emitters are investigated for high-performance thermophotovoltaic (TPV) systems. After building evaluation tools to find the highly efficient...

Context The use of the internet and technology as a medium for delivering online nutrition education (ONE) has increased; however, evidence-based studies exploring factors that contribute to best practices in online interventions have not emerged. Objective The purpose of this systematic review was to identify factors that contributed to successful ONE interventions in relation to research studies published between 2009 and 2018. Data sources Following the PRISMA guidelines, relevant studies were identified through PubMed, Medline, Web of Science, Science Direct, and Education Resources Information Center (ERIC) databases. Data extraction Five authors screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and extracted the data from the articles. Data analysis Twenty-seven studies were included: 21 studies were website-based, 3 were delivered through smartphone application, 2 were delivered as online courses, and 1 used text messages. Tailored messages/feedback, interaction between participants and investigators, identification of specific behaviors, use theory, adequate duration, and alignment between stated objectives and activities were factors that contributed to successful online interventions, while comparison bias and the lack of specific details on duration and dosage, tracking system, objective outcome measurements, and follow-up were factors that may have interfered with successful ONE interventions. Conclusions The findings underscore the importance of developing ONE intervention designs that utilize factors unique to online platforms for effective interventions aimed at behavior change.

1990년대부터 정부는 다양한 마을공동체 사업을 시행하여 농가소득 증대는 물론 농촌에 잠재되어 있던 공동체 의식을 촉진하고자 하고 있다. 그러나 모든 사업이 성공적인 결과를 가져오지 않았고 이에 무엇이 마을공동체 사업에 중요한 영향을 미치는지에 관한 연구가 다양하게 진행 되었다. 연구결과 마을리더의 역량, 신념, 추진력 등이 공동요인으로 발견되었고 특히 변화된 농촌상황에서 마을리더의 전문성이 강조되었다. 현재 농촌마을의 리더 중 46.2%가 귀농·귀촌인으로서 마을공동체 사업의 새로운 리더로 부각되고 있다. 그러나 귀농·귀촌리더와 관련한 연구는 전혀 이루어지지 않고 있다. 이에 따라 본 연구는 귀농·귀촌리더가 실제 마을공동체 사업에서 어떠한 역할을 하고 있는지 사례연구를 진행 하였고 다음과 같은 결과를 도출하였다. 첫째, 귀농·귀촌인으로서의 특성이 마을일에 영향을 주었음을 알 수 있었다. 활동력 있는 젊은 연령대, 도시민의 시각을 가진 객관적 시선, 숙련된 정보화기술력 등이 영향을 준 것이다. 둘째, 귀농·귀촌리더에게는 전문성이라는 지도자로서의 역할도 중요하지만 지도자의 봉사정신, 희생정신과 같은 지도자의 태도가 바탕이 되어야 함을 알 수 있었다. 셋째, 귀농·귀촌리더의 역할은 농촌마을에 흐려졌던 공동체성을 다시 살아나게 만들었음을 발견하였다. 사업이 진행되며 주민들의 소득이 높아지자 주민들에게 다시금 마을에 대한 애착과 공동체성이 살아나게 된 것이다. 결국 귀농·귀촌리더는 원주민과 다른 시선으로 마을을 봄으로써 마을의 강점과 약점을 객관적으로 파악할 수 있고, 농사와 관련된 기술은 부족하더라도 정보화활용기술은 뛰어나기 때문에 원주민과 협력한다면 마을에 상승효과를 불러일으킬 수 있으며, 농촌마을의 공동체성을 살아나게 하는 역할을 하고 있다.

We examine how donors influence nonprofit long-term product innovation by estimating a fixed-effects model using longitudinal data on a sample of nonprofit organizations. Innovation requires multiyear funding, but some donations to nonprofit organizations are a transient source of funding. Consistently, we find that when nonprofit organizations increasingly rely on donations from external private sources of funding, long-term innovation declines. However, as the nonprofit organization generates revenue from more predictable relational customers, concern associated with transient donations is attenuated. Moreover, in contrast to dependence on external donations deterring innovation, when a nonprofit grows their donor network, it increasingly emphasizes the long-term innovative interests of donors. The donor network offers social capital that provides managers with confidence and access to new information necessary to pursue innovation.

Purpose: To evaluate the efficacy and safety of a novel topical cyclosporin A 0.05% nanoemulsion in comparison with a conventional emulsion in primary Sjogren's syndrome dry eyes.Methods: Prospective, randomized, double-blinded study was conducted.Results: Corneal and conjunctival staining score was improved in both groups, with a faster change noted in the nanoemulsion group at 12 weeks (p < 0.05). Tear film break-up time was significantly improved in the nanoemulsion group at 12 weeks (p < 0.05), while ocular surface disease index score was improved in both groups without a difference at 12 weeks. Schirmer I value and goblet cell grade did not change in both groups. IL-6 and MMP-9 were significantly decreased in both groups at 12 weeks.Conclusions: Both nanoemulsion and conventional cyclosporin A improved ocular signs, symptoms, and conjunctival inflammation. However, the novel cyclosporin A nanoemulsion showed faster improvement of ocular surface staining scores than the conventional emulsion.

The survival rate of patients with cancer has been increasing because of the sustained anticancer effect of new drugs, such as immune checkpoints inhibitors (ICI). Unlike the existing cytotoxic chemotherapies, immunotherapy causes immune system disturbance, such as hypothyroidism. Comparative studies on hypothyroidism following administration of ICI alone and in combination with other drugs are scarce. Therefore, we investigated the incidence of hypothyroidism after ICI in patients with cancer using a national population-based database.Using the claims data from the Health Insurance Review and Assessment service in Korea, we retrospectively investigated patients with cancer who received chemotherapy between January 1, 2014 and February 28, 2021.Of all patients with cancer (n = 665,445) who received all kinds of chemotherapy, those who have received ICI accounted for 1.91 %. Compare with cytotoxic chemotherapy and angiogenesis inhibitors (AIs), ICI was associated with earlier (236.1 ± 248.4 vs. 811.1 ± 661.7, P 0.01) and more frequent (7.7 % vs. 4.4 %, P 0.01) occurrence of hypothyroidism, as well as an increased risk of developing hypothyroidism (odds ratio [OR] 1.69, 95 % confidence interval [CI] 1.58-1.80). However, the incidence of grade 2 or higher hypothyroidism was similar in both groups of patients who received ICI (3.3 %) and AI (3.1 %). The incidence of hypothyroidism was 4.4 times higher in patients who received both AI and ICI than in those who were treated with ICI alone (OR 4.41, 95 % CI 3.40-5.71).This study showed a synergistic effect in patients who received multiple administrations of a drug that might be associated with thyroid dysfunction. Therefore, special attention should be paid to the treatment-related side effects when using drugs, such as AIs, concomitant with ICI treatment.

Radiation-induced colitis is a common clinical problem after radiation therapy and accidental radiation exposure. Myeloid-derived suppressor cells (MDSCs) have immunosuppressive functions that use a variety of mechanisms to alter both the innate and the adaptive immune systems. Here, we demonstrated that radiation exposure in mice promoted the expansion of splenic and intestinal MDSCs and caused intestinal inflammation due to the increased secretion of cytokines. Depletion of monocytic MDSCs using anti-Ly6C exacerbated radiation-induced colitis and altered the expression of inflammatory cytokine IL10. Adoptive transfers of 0.5 Gy-derived MDSCs ameliorated this radiation-induced colitis through the production IL10 and activation of both STAT3 and SOCS3 signaling. Intestinal-inflammation recovery using 0.5 Gy-induced MDSCs was assessed using histological grading of colitis, colon length, body weight, and survival rate. Using in vitro co-cultures, we found that 0.5 Gy-induced MDSCs had higher expression levels of IL10 and SOCS3 compared with 5 Gy-induced MDSCs. In addition, IL10 expression was not enhanced in SOCS3-depleted cells, even in the presence of 0.5 Gy-induced monocytic MDSCs. Collectively, the results indicate that 0.5 Gy-induced MDSCs play an important immunoregulatory role in this radiation-induced colitis mouse model by releasing anti-inflammatory cytokines and suggest that IL10-overexpressing mMDSCs may be potential immune-therapy targets for treating colitis.

The primary cause of colorectal cancer (CRC) recurrence is increased distant metastasis after radiotherapy, so there is a need for targeted therapeutic approaches to reduce the metastatic-relapse risk. Dysregulation of the cell-surface glycoprotein podocalyxin-like protein (PODXL) plays an important role in promoting cancer-cell motility and is associated with poor prognoses for many malignancy types. We found that CRC cells exposed to radiation demonstrated increased TGFβ and PODXL expressions, resulting in increased migration and invasiveness due to increased extracellular matrix deposition. In addition, both TGFβ and PODXL were highly expressed in tissue samples from radiotherapy-treated CRC patients compared to those from patients without this treatment. However, it is unclear whether TGFβ and PODXL interactions are involved in cancer-progression resistance after radiation exposure in CRC. Here, using CRC cells, we showed that silencing PODXL blocked radiation-induced cell migration and invasiveness. Cell treatment with galunisertib (a TGFβ-pathway inhibitor) also led to reduced viability and migration, suggesting that its clinical use may enhance the cytotoxic effects of radiation and lead to the effective inhibition of CRC progression. Overall, the results demonstrate that downregulation of TGFβ and its-mediated PODXL may provide potential therapeutic targets for patients with radiotherapy-resistant CRC.

The detection of explosive nitroaromatic compounds has caused worldwide concern for human safety. In this study, we introduce a fluorescent biosensor based on porous biocompatible microspheres loaded with a bioreporter for the detection of nitroaromatic compounds. Poly(lactic-co-glycolic acid) microbeads were designed as biosensors embedded with the bacterial bioreporters. The genetically engineered bacterial bioreporter can express a green fluorescent protein in response to nitroaromatic compounds (e.g., trinitrotoluene and dinitrotoluene). The modified surface structure in microbeads provides a large surface area, as well as easy penetration, and increases the number of attached bioreporters for enhanced fluorescent signals of biosensors. Moreover, the addition of the M13 bacteriophage in open porous microbeads significantly amplified the fluorescence signal for detection by the π–π interaction between peptides in the M13 bacteriophage and nitroaromatic compounds. The modification of the surface morphology, as well as the genetically engineered M13 phage, significantly amplifies the fluorescence signal, which makes the detection of explosives easier, and has great potential for the stand-off remote sensing of TNT buried in the field.

Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular‐based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating β‐catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/β‐catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC., We provided targeting the DRD2/β‐catenin/ZEB1 signaling axis as a potentially promising therapeutic strategy for patients with CRC.

Mechanical forces are pervasive in the inflammatory site where dendritic cells (DCs) are activated to migrate into draining lymph nodes. For example, fluid shear stress modulates the movement patterns of DCs, including directness and forward migration indices (FMIs), without chemokine effects. However, little is known about the effects of biomechanical forces on the activation of DCs. Accordingly, here we fabricated a microfluidics system to assess how biomechanical forces affect the migration and activity of DCs during inflammation. Based on the structure of edema, we proposed and experimentally analyzed a novel concept for a microchip model that mimicked such vascular architecture. The intensity of shear stress generated in our engineered chip was found as 0.2–0.6 dyne/cm2 by computational simulation; this value corresponded to inflammation in tissues. In this platform, the directness and FMIs of DCs were significantly increased, whereas the migration velocity of DCs was not altered by shear stress, indicating that mechanical stimuli influenced DC migration. Moreover, DCs with shear stress showed increased expression of the DC activation markers MHC class I and CD86 compared with DCs under static conditions. Taken together, these data suggest that the biomechanical forces are important to regulate the migration and activity of DCs.

Obesity impairs wound healing with substantial alterations in skin inflammation. Patchouli alcohol (PA), extracted from patchouli, has been reported to ameliorate inflammation in various cell types. However, the effects of PA on inflammation and wound healing have not been reported to date. In the present study, we examined whether PA affects cutaneous wound healing in high fat diet (HFD)-fed mice and explored PA-mediated molecular mechanisms through in vitro experiments. We found that PA administration accelerated wound healing as well as ameliorates inflammation in skin of HFD-fed mice. PA treatment augmented AMP-activated protein kinase (AMPK) phosphorylation and TGFb1 expression. PA enhanced cell migration and suppressed inflammation in LPS-treated HaCaT cells. Further, PA increased dose-dependently AMPK phosphorylation as along with TGFb1 and cell migration markers expression. siRNA for AMPK or TGFb1 abrogated the effects of PA on cell migration and inflammation. TGFb1 siRNA mitigated PA-induced expression of cell migration markers. These results suggest that PA ameliorates wound healing via AMPK and TGFb1-mediated suppression of inflammation. In sum, PA can be used as a novel treatment strategy for wound healing in obesity or insulin resistance.

Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.

Capmatinib (CAP) has been used to treat metastatic non-small lung cancer (NSCL) and suppress inflammation. It causes hypoglycemia in NSCL patients. Therefore, it is expected that CAP improves inflammation-mediated insulin resistance due to its anti-inflammatory effect. However, the impacts of CAP on insulin signaling in skeletal muscle cells have not yet been fully elucidated. Herein, we investigated the effect of CAP on insulin resistance in palmitate-treated C2C12 myocytes and explored the related molecular mechanisms. We found that treatment of C2C12 myocytes with CAP reversed palmitate-induced impairment of insulin signaling and glucose uptake. CAP treatment ameliorated phosphorylation of inflammatory markers, including NFκB and IκB, in palmitate-treated C2C12 myocytes. Further, it augmented PPARδ expression and suppressed palmitate-induced p38 phosphorylation in a dose-dependent manner. siRNA-mediated suppression of PPARδ abolished the effects of CAP on palmitate-induced insulin resistance and inflammation as well as p38 phosphorylation. Therefore, it has been shown that CAP treatment ameliorates insulin resistance in palmitate-treated C2C12 myocytes via PPARδ/p38 signaling-mediated suppression of inflammation. These results may represent a novel therapeutic approach that could halt insulin resistance and type 2 diabetes.

In the original publication, affiliations 1 and 4 are the same. Yuri Seo's affiliaiton should also be changed to Yongin Severance Hospital.

Valdecoxib (VAL), a non-steroidal anti-inflammatory drug, has been widely used for treatment of rheumatoid arthritis, osteoarthritis, and menstrual pain. It is a selective cyclooxygenase-2 inhibitor. The suppressive effects of VAL on cardiovascular diseases and neuroinflammation have been documented; however, its impact on insulin signaling in skeletal muscle has not been studied in detail. The aim of this study was to investigate the effects of VAL on insulin resistance in mouse skeletal muscle. Treatment of C2C12 myocytes with VAL reversed palmitate-induced aggravation of insulin signaling and glucose uptake. Further, VAL attenuated palmitate-induced inflammation and endoplasmic reticulum (ER) stress in a concentration-dependent manner. Treatment with VAL concentration-dependently upregulated AMP-activated protein kinase (AMPK) and heat shock protein beta 1 (HSPB1) expression. In line with in vitro experiments, treatment with VAL augmented AMPK phosphorylation and HSPB1 expression, thereby alleviating high-fat diet-induced insulin resistance along with inflammation and ER stress in mouse skeletal muscle. However, small interfering RNA-mediated inhibition of AMPK abolished the effects of VAL on insulin resistance, inflammation, and ER stress. These results suggest that VAL alleviates insulin resistance through AMPK/HSPB1-mediated inhibition of inflammation and ER stress in skeletal muscle under hyperlipidemic conditions. Hence, VAL could be used as an effective pharmacotherapeutic agent for management of insulin resistance and type 2 diabetes.

Recently, there is a rapid increase in the incidence of obesity, a condition for which there are no effective therapeutic agents. Capmatinib (CAP), a novel mesenchymal-to-epithelial transition inhibitor, is reported to attenuate pro-inflammatory mediators and oxidative stress. In this study, the effects of CAP on lipogenesis in the adipocytes were examined. Treatment with CAP dose-dependently suppressed lipid accumulation in, and differentiation of, and increased lipolysis in, 3T3-L1 adipocytes. Additionally, CAP treatment augmented adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and FNDC5 expression in the adipocytes. Transfection with si-AMPK or si-FNDC5 mitigated the CAP-induced suppression of lipogenesis and enhanced lipolysis. Furthermore, transfection with si-FNDC5 mitigated the CAP-induced phosphorylation of AMPK. These results suggest that the anti-obesity effect of CAP is mediated through the irisin/AMPK pathway and that CAP is a novel therapeutic agent for obesity.